{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:32:21Z","timestamp":1784932341924,"version":"3.55.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Recent studies have underscored the importance of genetic factors in predicting COVID-19 susceptibility and severity. While cytokine storms are crucial in disease severity, genetic predisposition significantly influences immune responses. Our study examined genes related to SARS-CoV-2 invasion <jats:italic>(ACE2 rs2074192<\/jats:italic>) and interferon-induced immunity (<jats:italic>IFNAR2 rs2236757, TYK2 rs2304256, OAS1 rs10774671, OAS3 rs10735079<\/jats:italic>). Additionally, we investigated genes linked to Kawasaki disease (<jats:italic>CD40 rs4813003, FCGR2A rs1801274, CASP3 rs113420705<\/jats:italic>) that play roles in immunogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The pilot study, which involved 75 pediatric patients aged one month to 17 years [43 patients with active COVID-19, 17 children with multisystem inflammatory syndrome in children (MIS-C), and 15 healthy controls], was conducted in Ternopil, Ukraine. Gene polymorphism was studied for all patients. ELISA kits were used for interleukin studies, including Human IL-1\u03b2 (Interleukin 1 Beta), Human IL-6 (Interleukin 6), Human IL-8 (Interleukin 8), Human IL-12 (Interleukin 12), Human IFN-\u03b1 (Interferon Alpha), and Human TNF-\u03b1 (Tumor Necrosis Factor Alpha). Statistical analysis was performed using IBM SPSS Statistics 21 and GraphPad Prism 8.4.3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis identified significant gene-cytokine associations in pediatric COVID-19 patients. The <jats:italic>ACE2 rs2074192<\/jats:italic> T allele correlated with increased IL-1\u03b2, IL-6, IL-8, and TNF-\u03b1. The <jats:italic>IFNAR2 rs2236757<\/jats:italic> A allele was linked to elevated IL-1\u03b2 and IL-12 levels and low IFN-\u03b1 levels, while <jats:italic>OAS1 rs10774671<\/jats:italic> A allele carriers also exhibited lower IFN-\u03b1 levels. <jats:italic>OAS1 rs10774671<\/jats:italic> was prognostically crucial for determining IL-8 levels in children infected with SARS-CoV-2. <jats:italic>OAS3<\/jats:italic> gene polymorphism <jats:italic>rs10735079<\/jats:italic> was associated with changes in IL-6 levels, precisely a high level. The <jats:italic>CD40 rs4813003<\/jats:italic> T allele increased IFN-\u03b1 levels, while carriers of allele C had higher levels of IL-12. The results of our study revealed a correlation between IL-8 levels and the <jats:italic>FCGR2A<\/jats:italic> gene polymorphism <jats:italic>rs1801274<\/jats:italic> (A\/G). The <jats:italic>CASP3<\/jats:italic> gene polymorphism <jats:italic>rs113420705<\/jats:italic> led to an increase in IL-6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings enhance our understanding of pediatric COVID-19 and may hold promise for developing targeted interventions and providing a personalized medical approach for each patient.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1523627","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:45:59Z","timestamp":1740379559000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The influence of genetic polymorphisms on cytokine profiles in pediatric COVID-19: a pilot 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